A “State-of-the-Art Lecture” held this week at the 74th Scientific Sessions of the American Diabetes Association discussed the ineffectiveness of using antioxidant therapy in treating diabetes, and its harmful effects, which could include kidney disease and other complications. The findings presented were based on growing evidence that stimulating mitochondrial function and superoxide production resulted in markers that indicated renal, cardiovascular, and nerve dysfunction

The findings were presented by Dr. Kumar Sharma, director of the Center for Renal Translational Medicine, Division of Nephrology-Hypertension and the Institute of Metabolomic Medicine. In a press release, he said, "Scientists have long hypothesized that oxidative stress underlies diabetic complications and is driven by mitochondrial superoxide production and subsequent free radical damage to proteins and DNA. However, clinical trials to date have failed to demonstrate a benefit for antioxidant approaches and in some cases, such antioxidants have even increased mortality." 

Studies have suggested that oxidative stress causes tissue damage through its involvement in pancreatic cell dysfunction. In theory, antioxidants like N-acetyl-L-cysteine (NAC), and vitamins C and E are supposed to treat diabetes by protecting the pancreatic cells from oxidative damage and cell death, while preserving the amounts of insulin. However, this may not be the case after all. 

"Data from multiple independent investigations, including clinical metabolomics studies, now suggest that in response to excess calories, mitochondrial activity is actually reduced in target tissues for diabetes complications, and such persistent reduction may lead to the release of pro-inflammatory and pro-fibrotic cytokines and subsequent organ dysfunction," Sharma said. "Moreover, approaches that restore mitochondrial function and mitochondrial superoxide production via exercise, caloric restriction, and medications should help promote tissue healing."

Essentially, what Sharma is saying is that while superoxide production is beneficial, taking antioxidants to promote its production is not. Additionally, he noted that in independent studies in humans, pretreating participants with antioxidants (vitamins C and E) before exercise led to a loss in exercise's protective benefits regarding insulin resistance. 

"The new insights relating to the benefits of mitochondrial superoxide production, termed 'mitochondrial hormesis,' has raised many new exciting questions on the mechanisms linking mitochondrial superoxide production to beneficial effects," Sharma said in the release. "One potential link is that mitochondrial superoxide stimulates the master energy sensor AMPK, which when activated can suppress inflammation and fibrosis. The new theory is also a major boost for drugs that target and support mitochondrial function as potential treatments for diabetic complications and perhaps many other chronic diseases."